The Predictive Ability of MAGGIC Score After Coronary Artery Bypass Grafting: A Comparative Study

Introduction The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) are validated scoring systems for short-term risk estimation after coronary artery bypass grafting (CABG). The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score is originally aimed to estimate mortality in heart failure patients; however, it has showed a similar power to predict mortality after heart valve surgery. In this study, we sought to evaluate whether MAGGIC score may predict short and long-term mortality after CABG and to compare its power with EuroSCORE II and STS scoring systems. Methods Patients who underwent CABG due to chronic coronary syndrome at our institution were included in this retrospective study. Follow-up data were used to define the predictive ability of MAGGIC and to compare it with STS and EuroSCORE-II for early, one-year, and up to 10-year mortality. Results MAGGIC, STS, and EuroSCORE-II scores had good prognostic power, moreover MAGGIC was better for predicting 30-day (area under the curve [AUC]: 0.903; 95% confidence interval [CI]: 0.871-0.935), one-year (AUC: 0.931; 95% CI: 0.907-0.955), and 10-year (AUC: 0.923; 95% CI: 0.893-0.954) mortality. MAGGIC was found to be an independent predictor to sustain statistically significant association with mortality in follow-up. Conclusion MAGGIC scoring system had a good predictive accuracy for early and long-term mortality in patients undergoing CABG when compared to EuroSCORE-II and STS scores. It requires limited variables for calculation and still yields better prognostic power in determining 30-day, one-year, and up to 10-year mortality.


INTRODUCTION
Coronary artery disease (CAD) is the leading cause of death worldwide. The management of CAD has transformed significantly as a result of improvements in both medical and surgical therapies as well as percutaneous revascularization (percutaneous coronary intervention [PCI]) techniques. Currently, PCI and coronary artery bypass grafting (CABG) are the main treatment options for revascularization in which decision is made according to the risk stratification specified by the guidelines [1] . With regards to CABG, it is crucial to identify risk groups to optimize perioperative care of patients undergoing cardiac surgery and their postoperative follow-up. For the short-term mortality and morbidity risk estimation, several scoring systems were developed including the most widely used European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) scoring systems [2][3][4] . On the other hand, the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) is a recently developed risk scoring system which originally aimed to estimate mortality in heart failure patients [5] . The MAGGIC score was also investigated in transcatheter aortic valve implantation (TAVI) and heart valve surgery patients which revealed to have similar power to predict mortality in heart valve surgery and was shown as an independent predictor of all-cause death in TAVI patients [6][7][8] . The EuroSCORE II involves 18 clinical and laboratory parameters while the calculation of the STS score requires as many as 65 variables, which may not always be available in daily practice. Consequently, the complexity of these conventional scores justifies the need for a pragmatic and simple risk scoring system. The MAGGIC risk score consists of 13 simple variables including age, sex, ejection fraction (EF), systolic blood pressure, body mass index (BMI), serum creatinine level, New York Heart Association (NYHA) class, smoking status, presence of heart failure, chronic obstructive pulmonary disease (COPD), and diabetes, as well as use of beta-blockers and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB). The prognostic value of MAGGIC score has not been studied in CABG patients. In this study, we sought to evaluate  denotes patients who survived one year after the surgery, where  Control III group indicates those who survived up to 10 years after  CABG.  The EuroSCORE II definitions were used for preoperative  characteristics, including COPD, peripheral artery disease (PAD), critical preoperative state, left ventricular EF, and pulmonary hypertension (HT), and categories for renal impairment using creatinine clearance or dialysis [3] . Furthermore, the MAGGIC risk score consists of 13 simple variables including age, sex, EF, systolic blood pressure, BMI, serum creatinine level, NYHA class, smoking status, presence of heart failure, COPD, and diabetes, as well as use of beta-blockers and ACEI/ARB. Variables were retrieved from admission information. Transthoracic echocardiography was performed in all patients (Vivid S70; GE Medical System, Horten, Norway), and left ventricular EF was measured using Simpson's method. Heart failure was graded using the NYHA functional classification [9] . HT was defined as prescribed medications for lowering blood pressure, any measurement > 140/90 mmHg prior to operation, and/or a previous formal diagnosis [10] . Stroke was defined as any history of neurological deficits lasting > 24 hours that resulted from impaired cerebral blood flow [11] . A fasting blood sugar level ≥ 126 mg/dL (7.0 mmol/L) or use of antidiabetic medicine was indicative of diabetes mellitus (DM) [12] .
The primary endpoint of this study was assessment of 30-day mortality and the secondary endpoints were one-year and up to 10-year mortality during the follow-up.

Statistical Analysis
Continuous variables were presented as mean ± standard deviation or median and interquartile range (IQR), as appropriate. Dichotomous variables were defined as percentages and numbers. In order to stratify groups, patients were divided into two groups according to the median value of MAGGIC risk score as low and high MAGGIC groups. Chi-square test was used to compare the differences between two groups for categorical variables, and Student's t test for continuous variables. The Kaplan-Meier test was used to evaluate the incidence of all-cause death after CABG, and log-rank test was used to compare the difference of survival between two MAGGIC groups. Confounders in multivariate analysis were determined based on clinical significance. Receiver operating characteristic [ROC] curve analysis was performed to examine the discriminating powers of MAGGIC, STS, and EuroSCORE risk scores. The association between the level of risk of death predicted by a score and the patient's mortality, adjusted for the other scores, was tested by logistic regression. The calibration of the models was evaluated by the Hosmer-Lemeshow test. Statistical analysis was performed using the IBM Corp. Released 2012, IBM SPSS Statistics for Windows, version 21.0, Armonk, NY: IBM Corp. software. A P-value was two-sided, and a P-value < 0.05 was considered statistically significant.

RESULTS
A total of 729 patients were evaluated and after exclusion of 132 patients who underwent emergency CABG, concurrent heart valves and/or carotid artery surgery, patients with missing data, and those lost to follow-up, finally 597 patients were analyzed ( Figure 1).

DISCUSSION
To our best knowledge, this is the first study designed to assess clinical validation of the MAGGIC risk score to predict all-cause death after CABG. This single-center retrospective study showed that MAGGIC, STS, and EuroSCORE scores had good prognostic power, and that MAGGIC score was better for predicting all-cause 30-day, one-year, and 10-year mortality risk. MAGGIC was found to be independent predictor to sustain statistically significant association with mortality in follow-up according to regression analyses. STS score and EuroSCORE II are validated and widely used risk scores to predict perioperative morbidity and mortality after cardiac surgery. Whereas, both scoring systems consist of multiple variables that may not be readily available, such as coronary artery anatomy or valve pathologies on echocardiography for STS score and presence and specific degree of pulmonary HT or extracardiac arteriopathy for EuroSCORE II [3,4] . For these reasons, these missing variables negatively affect the predictive ability of STS score and EuroSCORE II for perioperative risk estimation [13] . Stratifying high risk patients who require close monitoring are crucial for patient management and to raise the assignments of sources.
In this context, MAGGIC can be a viable alternative to these established risk prediction models in CABG. MAGGIC, with only 13 key demographic variables, provides a comparatively simple and user-friendly tool for clinicians, qualities that can extend its usefulness beyond its limits, the original heart failure population from which it is derived [8,14,15] . However, its prognostic importance has also been demonstrated in various cardiac diseases other than heart failure. The MAGGIC risk score has been identified as a valid   [7] . In another study, the MAGGIC score predicted all-cause death, especially in the transcatheter aortic valve replacement population with a high risk of STS [6] . The present study contributed more on the substantial literature by demonstrating the novel benefit of MAGGIC risk score in CABG patients. Patients with a high MAGGIC risk score compared to the patients in the lower values were demonstrated to have higher risk of short and longterm death. Age, EF, systolic blood pressure, BMI, creatinine level, NYHA class, sex, history of DM, COPD, smoking status, diagnosis of heart failure (≥ 18 months), and use of beta-blockers and ACEI/ARB are variables obligatory to calculate MAGGIC score. Age, EF, and renal function are known risk factors for CABG surgery [16][17][18][19][20] . Patients with DM tend to have advanced CAD, and CABG is a broadly applied treatment. However, short-term procedural success rates are similar, death and adverse cardiac events are more common in diabetic patients after CABG surgery [21,22] . COPD is a common condition in cardiac patients and was found to be related with increased postoperative complications and early death in severe cases [23,24] . Since these are the main components of MAGGIC score, this score offers to evaluate most of the main risk factors in a simple way. Additionally, MAGGIC risk score evaluates patient's betablocker and ACEI/ARB usage, which are cornerstone of heart failure therapy. Beta-blockers are also recommended in treatment of CAD to reduce mortality, arrythmia, and ischemic events. Patients on beta-blocker or antihypertensive therapy, including ACEI/ARB, are in the lower risk for mortality according to our results. Moreover, lower beta-blocker usage was detected as an independent risk factor related with 10-year mortality. This finding emphasizes the importance of adequate use of guideline directed treatment. CAD severity and location are factors related with CABG success that are evaluated both in EuroSCORE II and STS scores. MAGGIC risk score was found to foresee mortality both at the early period and follow-up better than EuroSCORE II and STS scores, although it does not include the variable regarding coronary anatomy. This finding may emphasize the importance of patient-related hemodynamic factors and comorbidities. Likewise, experience of surgeon and hospital volume are inevitable factors that may alter the success of procedure, but these factors are nonapplicable to any risk score model [25,26] .
The EuroSCORE II and STS scores were designed for in-hospital risk prediction, however the studies for their power for long-term mortality estimation have shown that their predictive ability is still acceptable for two years, but decreases year by year after that [27] . These scores were based on collected data at the beginning of 1990s, nevertheless, patient characteristics and surgical techniques changed over time. Another issue is that the study population consisted of both elective and urgent/emergency cases, however, we excluded emergency cases and evaluated patients who are candidate for elective CABG. According to our results, MAGGIC score was better than either EuroSCORE II and STS scores in terms of predicting mortality at early stage and follow-up both at one year and 10 years after CABG, at the same time EuroSCORE II was found to be an independent predictor of mortality in one-year mortality but not in follow-up. Our results indicating early mortality were a higher than expected incidence [28,29] . We collected data between 2011 and 2013. The

Limitations
First, this is a single-center retrospectively designed study; multicenter and prospectively designed studies would be better to avoid selection or definition bias. Second, the term 30-day mortality includes mortality events both in hospital and after discharge at the 30th postoperative day. However, separating the events may help risk scores to predict them. And third, postoperative complications could not be evaluated. Patients presenting with acute coronary syndromes are usually high-risk patients and may present with cardiogenic shock. We excluded those patients, however, prospective studies including acute coronary syndrome patients will give additional information in this subgroup. Also, our study population mostly involved low-risk patients according to EuroSCORE II and STS scores; designing prospective studies including higher risk patients would be more informative.

CONCLUSION
The results of this study indicated that the MAGGIC scoring system, which has been originally developed for the prediction of mortality in heart failure patients, also had a good predictive accuracy for early and long-term mortality in patients undergoing CABG when compared to the EuroSCORE II and STS scoring systems. Besides, the MAGGIC score requires limited variables for calculation and still yields better prognostic power in determining 30-day, oneyear, and up to 10-year mortality. Thus, the MAGGIC score may aid clinicians to easily assess mortality risk in these patients. However, further studies with a larger patient population, particularly those with high risk, are needed to validate this scoring system.